Nanostructures comprising cobalt porphyrin-phospholipid conjugates and polyhistidine-tags

Abstract

The present disclosure provides nanostructures (e.g., monolayer or bilayer nanostructures) comprising porphyrins with cobalt chelated thereto such that the cobalt metal resides within monolayer or bilayer in the porphyrin macrocycle. The nanostructures can have presentation molecules with a histidine tag attached thereto, such that at least a part of the his-tag is within the monolayer or bilayer and coordinated to the cobalt metal core and the presentation molecules are exposed to the outside of the nanostructures. The nanostructures can further comprise a cargo. The nanostructures can be used to deliver the cargo to an individual.

What is claimed is: 
     
       1. A liposome comprising:
 a) a bilayer, wherein the bilayer comprises:
 i) phospholipid, and 
 ii) porphyrin having cobalt coordinated thereto forming cobalt-porphyrin; and 
 
 b) a polyhistidine-tagged presentation molecule, wherein at least a portion of the polyhistidine tag resides in the hydrophobic portion of the monolayer or the bilayer and one or more histidines of the polyhistidine tag are coordinated to the cobalt in the cobalt-porphyrin, 
 
       wherein at least a portion of the polyhistidine-tagged presentation molecule is exposed to the outside of the liposome, and wherein the liposome encloses an aqueous compartment. 
     
     
       2. The liposome of  claim 1 , wherein the cobalt porphyrin is conjugated to a phospholipid to form a cobalt porphyrin-phospholipid conjugate. 
     
     
       3. The liposome of  claim 2 , wherein the cobalt porphyrin-phospholipid conjugate makes up from 1 to 25 mol % of the monolayer or the bilayer. 
     
     
       4. The liposome of  claim 3 , wherein the cobalt porphyrin-phospholipid conjugate makes up from 5 to 10 mol % of the monolayer or bilayer. 
     
     
       5. The liposome of  claim 1 , wherein the bilayer further comprises cholesterol. 
     
     
       6. The liposome of  claim 1 , wherein the bilayer further comprises phosphatidylserine and, optionally, cholesterol. 
     
     
       7. The liposome of  claim 1 , wherein the polyhistidine-tag comprises 6 to 10 histidine residues. 
     
     
       8. The liposome of  claim 1 , wherein size of the liposome is 50 nm to 200 nm. 
     
     
       9. The liposome of  claim 1 , wherein the liposome comprises a cargo and wherein at least a portion of the cargo resides in the aqueous compartment. 
     
     
       10. The liposome of  claim 1 , wherein the presentation molecule is a peptide of from 4 to 50 amino acids, said number of amino acids not including the histidines of the his-tag. 
     
     
       11. The liposome of  claim 1 , wherein the presentation molecule is a protein from 4 to 500 kDa. 
     
     
       12. The liposome of  claim 1 , wherein the presentation molecule is an antigenic molecule and the bilayer further comprises an adjuvant incorporated therein. 
     
     
       13. The liposome of  claim 12 , wherein the adjuvant is attenuated lipid A derivative. 
     
     
       14. The liposome of  claim 13 , wherein the attenuated lipid A derivative is monophosphoryl lipid A or 3-deacylated monophosphoryl lipid A. 
     
     
       15. A nanostructure comprising:
 a) a core; and 
 b) a monolayer or a bilayer on said core, wherein the monolayer or bilayer comprises:
 i) phospholipid monomers, and 
 ii) porphyrin having cobalt coordinated thereto forming cobalt-porphyrin; and 
 
 c) a polyhistidine-tagged presentation molecule, wherein at least a portion of the polyhistidine tag resides in the hydrophobic portion of the monolayer or the bilayer, one or more histidines of the polyhistidine tag are coordinated to the cobalt in the cobalt-porphyrin, and at least a portion of the polyhistidine-tagged presentation molecule is exposed on the outside of the nanostructure. 
 
     
     
       16. The nanostructure of  claim 15 , wherein the core is a gold nanoparticle. 
     
     
       17. A method of targeted delivery of a cargo comprising:
 a) administering to an individual a composition comprising the liposomes of  claim 9  in a pharmaceutical carrier; 
 b) after a suitable period of time to allow the liposomes to reach a desired location in the individual, exposing the liposomes to near infrared radiation of a wavelength from 650 to 1000 nm to effect release of the cargo from the liposomes. 
 
     
     
       18. The method of  claim 17 , wherein the individual is a human or non-human animal. 
     
     
       19. A method for generating an immune response in a host individual comprising administering to the individual a composition comprising the liposomes of  claim 1  in a pharmaceutical carrier, wherein the presentation molecule comprises an immunogenic epitope. 
     
     
       20. The method of  claim 19 , wherein the presentation molecule is a peptide, polypeptide or protein derived from a pathogenic microorganism. 
     
     
       21. The method of  claim 20 , wherein the individual is a human or non-human animal.